PDBsum entry 2hi3

Transcription

PDB id: 2hi3

Contents

Protein chain

73 a.a. *

* Residue conservation analysis

PDB id:

2hi3

Name:

Transcription

Title:

Solution structure of the homeodomain-only protein hop

Structure:

Homeodomain-only protein. Chain: a. Synonym: hop, homeobox-only protein, odd homeobox protein 1, mob1. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

NMR struc:

20 models

Authors:

J.P.Mackay,H.Kook,J.A.Epstein,R.J.Simpson,W.W.Yung

Key ref:

H.Kook et al. (2006). Analysis of the structure and function of the transcriptional coregulator HOP. Biochemistry, 45, 10584-10590. PubMed id: 16939210 DOI: 10.1021/bi060641s

Date:

28-Jun-06 Release date: 02-Jan-07

Protein chain

Q8R1H0  (HOP_MOUSE) -  Homeodomain-only protein from Mus musculus

Seq: 73 a.a.

Struc: 73 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1021/bi060641s

Biochemistry 45:10584-10590 (2006)

PubMed id: 16939210

Analysis of the structure and function of the transcriptional coregulator HOP.

H.Kook, W.W.Yung, R.J.Simpson, H.J.Kee, S.Shin, J.A.Lowry, F.E.Loughlin, Z.Yin, J.A.Epstein, J.P.Mackay.

ABSTRACT

Homeodomain-only protein (HOP) is an 8-kDa transcriptional corepressor that is essential for the normal development of the mammalian heart. Previous studies have shown that HOP, which consists entirely of a putative homeodomain, acts downstream of Nkx2.5 and associates with the serum response factor (SRF), repressing transcription from SRF-responsive genes. HOP is also able to recruit histone deacetylase (HDAC) activity, consistent with its ability to repress transcription. Unlike other classic homeodomain proteins, HOP does not appear to interact with DNA, although it has been unclear if this is because of an overall divergent structure or because of specific amino acid differences between HOP and other homeodomains. To work toward an understanding of HOP function, we have determined the 3D structure of full-length HOP and used a range of biochemical assays to define the parts of the protein that are functionally important for its repression activity. We show that HOP forms a classical homeodomain fold but that it cannot recognize double stranded DNA, a result that emphasizes the importance of caution in predicting protein function from sequence homology alone. We also demonstrate that two distinct regions on the surface of HOP are required for its ability to repress an SRF-driven reporter gene, and it is likely that these motifs direct interactions between HOP and partner proteins such as SRF- and HDAC-containing complexes. Our results demonstrate that the homeodomain fold has been co-opted during evolution for functions other than sequence-specific DNA binding and suggest that HOP functions as an adaptor protein to mediate transcriptional repression.